Contribution of an alveolar cell of origin to the high-grade malignant phenotype of pregnancy-associated breast cancer.

Pregnancy-associated breast cancers (PABCs) are tumors diagnosed during pregnancy or up to 5 years following parturition, and are usually high-grade, connective tissue-rich, and estrogen receptor (ER)/progesterone receptor-negative. Little is known about the cellular origin of PABCs or the mechanisms by which PABCs are initiated. Using the RCAS retrovirus to deliver the ErbB2 oncogene into the mammary epithelium of our previously reported MMTV-tva transgenic mice, we detected high-grade, poorly differentiated, stroma-rich and ER-negative tumors during pregnancy and lactation. These high-grade and stroma-rich tumors were less frequent in involuted mice or in age-matched nulliparous mice. More importantly, by generating a WAP-tva transgenic line for expression of ErbB2 selectively in WAP(+) mammary alveolar cells, we found that tumors had similar morphological phenotypes (high grade, poorly differentiated, stroma-rich and ER-negative), irrespective of the time since pregnancy and even in the absence of pregnancy. These data suggest that PABCs arise preferentially from an alveolar cell population that expands during pregnancy and lactation. This somatic mouse model may also be useful for preclinical testing of new prophylactic and therapeutic strategies against PABC

Association between cognitive performance and cortical glucose metabolism in patients with mild Alzheimer's disease

Background: Neuronal and synaptic function in Alzheimer's disease (AD) is measured in vivo by glucose metabolism using positron emission tomography (PET). Objective: We hypothesized that neuronal activation as measured by PET is a more sensitive index of neuronal dysfunction than activity during rest. We investigated if the correlations between dementia severity as measured with the Mini Mental State Examination (MMSE) and glucose metabolism are an artifact of brain atrophy. Method: Glucose metabolism was measured using {[}F-18]fluorodeoxyglucose PET during rest and activation due to audiovisual stimulation in 13 mild to moderate AD patients (MMSE score >= 17). PET data were corrected for brain atrophy. Results: In the rest condition, glucose metabolism was correlated with the MMSE score primarily within the posterior cingulate and parietal lobes. For the activation condition, additional correlations were within the primary and association audiovisual areas. Most local maxima remained significant after correcting for brain atrophy. Conclusion: PET activity measured during audiovisual stimulation was more sensitive to functional alterations in glucose metabolism in AD patients compared to the resting PET. The association between glucose metabolism and MMSE score was not dependent on brain atrophy. Copyright (C) 2005 S. Karger AG, Basel

Prognostic relevance of a T-type calcium channels gene signature in solid tumours: A correlation ready for clinical validation

BackgroundT-type calcium channels (TTCCs) mediate calcium influx across the cell membrane. TTCCs regulate numerous physiological processes including cardiac pacemaking and neuronal activity. In addition, they have been implicated in the proliferation, migration and differentiation of tumour tissues. Although the signalling events downstream of TTCC-mediated calcium influx are not fully elucidated, it is clear that variations in the expression of TTCCs promote tumour formation and hinder response to treatment.MethodsWe examined the expression of TTCC genes (all three subtypes; CACNA-1G, CACNA-1H and CACNA-1I) and their prognostic value in three major solid tumours (i.e. gastric, lung and ovarian cancers) via a publicly accessible database.ResultsIn gastric cancer, expression of all the CACNA genes was associated with overall survival (OS) among stage I-IV patients (all pConclusionsAlterations in CACNA gene expression are linked to tumour prognosis. Gastric cancer represents the most promising setting for further evaluation

Experimental modulation of capsule size in Cryptococcus neoformans

Experimental modulation of capsule size is an important technique for the study of the virulence of the encapsulated pathogen Cryptococcus neoformans. In this paper, we summarize the techniques available for experimental modulation of capsule size in this yeast and describe improved methods to induce capsule size changes. The response of the yeast to the various stimuli is highly dependent on the cryptococcal strain. A high CO(2) atmosphere and a low iron concentration have been used classically to increase capsule size. Unfortunately, these stimuli are not reliable for inducing capsular enlargement in all strains. Recently we have identified new and simpler conditions for inducing capsule enlargement that consistently elicited this effect. Specifically, we noted that mammalian serum or diluted Sabouraud broth in MOPS buffer pH 7.3 efficiently induced capsule growth. Media that slowed the growth rate of the yeast correlated with an increase in capsule size. Finally, we summarize the most commonly used media that induce capsule growth in C. neoformans

An invisibility cloak using silver nanowires

In this paper, we use the parameter retrieval method together with an analytical effective medium approach to design a well-performed invisible cloak, which is based on an empirical revised version of the reduced cloak. The designed cloak can be implemented by silver nanowires with elliptical cross-sections embedded in a polymethyl methacrylate host. This cloak is numerically proved to be robust for both the inner hidden object as well as incoming detecting waves, and is much simpler thus easier to manufacture when compared with the earlier proposed one [Nat. Photon. 1, 224 (2007)].Comment: 7 pages, 4 figures, 2 table

Adaptive Filtering Enhances Information Transmission in Visual Cortex

Sensory neuroscience seeks to understand how the brain encodes natural environments. However, neural coding has largely been studied using simplified stimuli. In order to assess whether the brain's coding strategy depend on the stimulus ensemble, we apply a new information-theoretic method that allows unbiased calculation of neural filters (receptive fields) from responses to natural scenes or other complex signals with strong multipoint correlations. In the cat primary visual cortex we compare responses to natural inputs with those to noise inputs matched for luminance and contrast. We find that neural filters adaptively change with the input ensemble so as to increase the information carried by the neural response about the filtered stimulus. Adaptation affects the spatial frequency composition of the filter, enhancing sensitivity to under-represented frequencies in agreement with optimal encoding arguments. Adaptation occurs over 40 s to many minutes, longer than most previously reported forms of adaptation.Comment: 20 pages, 11 figures, includes supplementary informatio

Basal Forebrain Mediated Increase in Brain CRF is Associated with Increased Cholinergic Tone and Depression

Major depression is a devastating disease that generates significant suffering and cost. After controlling for the main effects of diagnosis and Cerebrospinal Fluid Corticotropin-Releasing Factor (CSF CRF), the interaction between CSF CRF and major depression disorder diagnosis was a significant predictor of basal forebrain cholinergic nuclei volume, but not of hippocampal volume. By investigating both markers concurrently in participants with and without depression, we describe the extent to which the interaction between CSF CRF levels and depression diagnosis is associated with the volume of the forebrain cholinergic nuclei and of the hippocampus. These results contribute to our understanding of the role of brain’s stress axis in depression

A linguistic approach to assess the dynamics of design team preference in concept selection

This paper addresses the problem of describing the decision-making process of a committee of engineers based upon their verbalized linguistic appraisals of alternatives. First, we show a way to model an individual’s evaluation of an alternative through natural language based on the Systemic-Functional Linguistics system of APPRAISAL. The linguistic model accounts for both the degree of intensity and the uncertainty of expressed evaluations. Second, this multi-dimensional linguistic model is converted into a scalar to represent the degree of intensity and a probability distribution function for the stated evaluation. Finally, we present a Markovian model to calculate the time-varying change in preferential probability, the probability that an alternative is the most preferred alternative. We further demonstrate how preferential probability toward attributes of alternatives correspond to preferential probability toward alternatives. We illustrate the method on two case studies to highlight the time-variant dynamics of preferences toward alternatives and attributes. This research contributes to process tracing in descriptive decision science to understand how engineers actually take decisions.National Science Foundation (U.S.) (Award CMMI-0900255